Polymeric nanoparticles: studies toward targeted drug delivery of HIV therapeutics and characterization of environmental impacts
Embargo Date
2027-01-29
OA Version
Citation
Abstract
Nanoparticles are often categorized as ‘primary’ or ‘secondary,’ depending on whether they are nanoscale in size by design or the result of an environmental weathering process, respectively. Primary polymeric nanoparticles have garnered significant attention for applications in nanomedicine and a wide range of consumer products, due in part to their tunable properties, large surface-to-volume ratio, and size complementarity with biological structures. For example, polymeric nanoparticles can be utilized as drug carriers with programmable release characteristics and engineered for tissue-specific targeting. However, it has become increasingly clear that the properties that make polymeric nanoparticles attractive for therapeutic use can have unintended consequences if they are released in large quantities into the environment. Secondary nanoplastics, formed from largely non-biodegradable plastic debris in the oceans, represent a significant hazard. Two aspects of this hazard are the cellular responses associated with the ingestion of nanoplastics and their role as vehicles for otherwise water-insoluble carcinogens. Herein, we explore the advantages of intentionally synthesized and well-characterized polymeric nanoparticles for drug delivery applications and highlight the urgent need to address the potential implications of nanoplastic pollution on the environment, animal life, and public health. Specifically, in the first part of this work, we demonstrated that well-established nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), emtricitabine (FTC) and tenofovir (TFV), can be linked to poly(amidoamine) (PAMAM) dendrimers to form prodrugs, which were subsequently co-loaded into monosialodihexosylganglioside (GM3)-coated poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-PCL) nanoparticles, enabling selective binding to CD169+ cells. This formulation maintained long-term human immunodeficiency virus type 1 (HIV-1) inhibition and provided sustained drug release for up to 42 days. Importantly, no detectable cytotoxicity or immunogenicity was observed, supporting its promise as a long-acting pre-exposure prophylaxis (PrEP) platform. In the second part of this work, we established an accelerated photochemical weathering model to probe the effects of photochemical weathering on the size, morphology, and chemical composition of nanoplastics derived from consumer plastics, and validated that the resulting degradation was consistent with plastics harvested from the oceans. Despite oxidation and mineral deposition, we showed that weathered nanoplastics retained a strong sorption capacity for polycyclic aromatic hydrocarbons (PAHs). Furthermore, we demonstrated that nanoplastics, with or without sorbed PAHs, were actively transported across intestinal model membranes and altered gene expression profiles.
Description
2026